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The researchers used site-specific mutagenesis to gain new insights into how the cofactor precursor is integrated into the enzyme and how individual amino acids are involved in anchoring and synthesis.

The paper, "Base editing mutagenesis maps functional alleles to tune human T cell activity," was published in Nature on December 13.

"Xiangyu's comprehensive study of the structure highlights the advantage that a targeted, structurally guided approach has over large and costly random mutagenesis screening."

“That is what we term lethal mutagenesis,” he adds.

The use of this technique could be seen as a weakness of Wang and co-workers’ approach, because unnatural-amino-acid mutagenesis is not suitable for all cell types, and can require substantial optimization for each application.